Strategies for Multilocus Linkage Analysis in Humans
G.M. Lathrop, J.M. Lalouel, C. Julier, J. Ott
Proceedings of the National Academy of Sciences of the United States of
America
81(11), 3443--3446 (1984 Jun)
Abstract
The increasing number of DNA polymorphisms characterized in humans
will soon allow the construction of fine genetic maps of human
chromosomes. This advance calls for a reexamination of current
methodologies for linkage analysis by the family method. We have
investigated the relative efficiency of two-point and three-point
linkage tests for the detection of linkage and the estimation of
recombination in a variety of situations. This led us to develop the
computer program LINKAGE to perform multilocus linkage analysis. The
investigation also enables us to propose a method of location scores
for the efficient detection of linkage between a disease locus, or a
new genetic marker, and a linkage group previously established from
a reference panel of families. The method is illustrated by an
application to simulated pedigree data in a situation akin to
Duchenne muscular dystrophy. These results show that considerable
economy and efficiency can be brought to the mapping endeavor by
resorting to appropriate strategies of detecting linkage and by
constructing the human genetic map on a common reference panel of
families.
